Exogenous prostaglandin E 2 inhibits TPA induced matrix metalloproteinase-9 production in MCF-7 cells

• Published in: Prostaglandins & other lipid mediators Vol. 73; no. 3; pp. 237 - 247
• Main Authors: Renò, F, Baj, G, Surico, N, Cannas, M
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2004
• Subjects: Breast cancer; EP4; MCF-7; Metastasis; MMP-9; PGE 2; TPA; TPA; MCF-7; PGE 2; EP4; Breast cancer; Metastasis; MMP-9
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2004.03.002

Elevated levels of prostaglandin E 2 (PGE 2) have been reported in many high metastatic human breast cancers, but no relationship between exogenous PGE 2 activity, expression of matrix metalloproteinases (MMPs) and metastasis in human tumor cells has been reported. The poorly invasive human breast cancer cell line MCF-7 was cultured for 24 h in the presence of both phorbol ester 12- O-tetradecanoylphorbol-13-acetate (TPA, 50 nM) and PGE 2 (1 μM) and the activity of MMP-9, one of the MMPs involved in metastasis, was measured, in growth medium by gelatin substrate zymography. TPA induced a strong production of MMP-9 while exogenous PGE 2 had no effect on the basal MMP-9 level, but inhibited the TPA induced enzyme expression and matrigel invasiveness. We showed that MCF-7 cells expressed EP2, EP3 and EP4 receptors for PGE 2 and that its action was probably mediated by EP4 receptor and adenylyl cyclase activation while cAMP dependent PKA was not involved in the process of inhibition of MMP-9 production. These findings suggest a possible inhibitory role for exogenous PGE 2 in the metastatic process development.